This invention relates to a screening test for cancerous and precancerous conditions and to a kit containing the components necessary for conducting the test.
Cancer is a major public health problem in the world. Even as pharmaceutical agents for the treatment of cancer are developed, early detection and prevention are still the best hope for combating this human tragedy. In U.S. Pat. No. 4,857,457 I claim and in Shamsuddin et al., Human Pathology, 19: 7-10, 1988, there is reported a screening test for colorectal cancer which can detect cancer of the large intestine employing rectal mucus. The mucus is reacted with the enzyme galactose oxidase by moistening a cellulose membrane filter, which had previously been impregnated with a phosphate buffer solution of the enzyme and then lyophilized, and then contacting the moistened cellulose membrane filter with a Metricel membrane filter bearing the mucus sample for 1-2 hours. The mucus-bearing membrane filter is then washed with distilled water for 1 minute, reacted with basic fuchsin for 15 minutes, washed in tap water for 10 minutes and then air dried.
This basic procedure, although simple, is limited to detecting rectocolon cancer and precancerous conditions. Moreover, it suffers from the serious deficiency that it has since been found by me that it is not specific to cancers of the large intestine, i.e., the marker disaccharide employed therein as predicative of rectocolon cancer is also present in rectal mucus when a cancerous or precancerous condition is present at another site of the body. Also the test as described therein is lengthy. Moreover, if a patient tests positive in this screening test, rather than being selectively predictive of rectocolon cancer, it in fact is predictive of virtually any cancerous or precancerous condition. If a patient tests negative by this screening test, it can mean either a biological negative, i.e., the patient does not have a cancerous or precancerous condition which releases a marker carbohydrate employed in the screening test, or it is technically negative, i.e., and insufficient mucus from the rectum was obtained in order to detect any marker carbohydrate present therein. The latter situation could mean a "false negative," the consequence of which could be dangerous to the person tested since any cancer present could continue to grow undetected because the negative results would give the patient and the patient's physician a false sense of security which might cause the patient or his/her physician to disregard symptoms that might otherwise be investigated if the negative results had not been obtained.
Another deficiency of this test is the known unstable nature of the basic fuchsin which is a critical component therein. According to the prior art, basic fuchsin must be prepared fresh and discarded after a week because of its instability. (Manual of Histological Staining Methods of the Armed Forces Institute of Pathology, Ed. 3, McGraw-Hill, New York, 1968, p. 159.) This makes it impossible to provide the materials required to conduct the screening test in kit form, since shipping, handling and storage of such kits would require a shelf life of at least six months and the instability of the basic fuchsin would preclude such a shelf life.
Finally, as noted above, the screening test as reported by me, Shamsuddin et al., Human Pathology, 1988, 19:7-10, in addition to the several hours of preparation for the lyophilization of galactose oxidase, employed more than two hours to obtain the results thereof, which makes the test impractical for mass screening of large segments of the population and effectively precludes reporting the test results to the individual tested before that individual leaves the test area, e.g., the doctor's office or a mobile laboratory.
Since most cancers in humans are believed to be the result of exposure to one or more environmental carcinogens which are excreted through the large intestine or urinary bladder, it can be expected that the carcinogen(s) and/or their metabolite(s) cause changes in those organs, in addition to causing corresponding changes simultaneously in the organ bearing the cancer and precancer. Precancer or precancerous conditions are those stages or diseases that render an individual highly susceptible to subsequent cancer (high risk symptomatic). Based on this hypothesis the presence of or threat of a cancerous or precancerous condition in the body of an individual, including but not restricted to the large intestine, can be detected accurately by the method of this invention initially using rectal mucus sampling, followed, if necessary, by sampling of other body fluids, such as secretions of breast, prostate, semen, uterine endocervix and vagina, mucus, sputum, bronchial or alveolar secretions, until the precise situs of the cancerous or precancerous condition is located, without the prior risk of false negatives which limited the value of this technique as a screening test, particularly as a field test, for the general population. The present invention eliminates false negative results which are obtained as a result of inadequate sampling, permits rapid testing for the presence of absence of precancer or cancer carbohydrate markers in about 15 minutes or less and ensures the stability of the critical components required to conduct the test for over one year. It also eliminates the "false positives" of U.S. Pat. No. 4,857,457, i.e., a positive test supposedly indicating a cancerous or precancerous condition in the rectocolon area but in fact is present in another area of the body.